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Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo – a post-hoc analysis of the BACE randomized controlled trial

BACKGROUND: In the BACE trial, a 3-month (3 m) intervention with azithromycin, initiated at the onset of an infectious COPD exacerbation requiring hospitalization, decreased the rate of a first treatment failure (TF); the composite of treatment intensification (TI), step-up in hospital care (SH) and...

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Autores principales: Vermeersch, Kristina, Belmans, Ann, Bogaerts, Kris, Gyselinck, Iwein, Cardinaels, Nina, Gabrovska, Maria, Aumann, Joseph, Demedts, Ingel K., Corhay, Jean-Louis, Marchand, Eric, Slabbynck, Hans, Haenebalcke, Christel, Vermeersch, Stefanie, Verleden, Geert M., Troosters, Thierry, Ninane, Vincent, Brusselle, Guy G., Janssens, Wim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819655/
https://www.ncbi.nlm.nih.gov/pubmed/31665017
http://dx.doi.org/10.1186/s12931-019-1208-6
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author Vermeersch, Kristina
Belmans, Ann
Bogaerts, Kris
Gyselinck, Iwein
Cardinaels, Nina
Gabrovska, Maria
Aumann, Joseph
Demedts, Ingel K.
Corhay, Jean-Louis
Marchand, Eric
Slabbynck, Hans
Haenebalcke, Christel
Vermeersch, Stefanie
Verleden, Geert M.
Troosters, Thierry
Ninane, Vincent
Brusselle, Guy G.
Janssens, Wim
author_facet Vermeersch, Kristina
Belmans, Ann
Bogaerts, Kris
Gyselinck, Iwein
Cardinaels, Nina
Gabrovska, Maria
Aumann, Joseph
Demedts, Ingel K.
Corhay, Jean-Louis
Marchand, Eric
Slabbynck, Hans
Haenebalcke, Christel
Vermeersch, Stefanie
Verleden, Geert M.
Troosters, Thierry
Ninane, Vincent
Brusselle, Guy G.
Janssens, Wim
author_sort Vermeersch, Kristina
collection PubMed
description BACKGROUND: In the BACE trial, a 3-month (3 m) intervention with azithromycin, initiated at the onset of an infectious COPD exacerbation requiring hospitalization, decreased the rate of a first treatment failure (TF); the composite of treatment intensification (TI), step-up in hospital care (SH) and mortality. OBJECTIVES: (1) To investigate the intervention’s effect on recurrent events, and (2) to identify clinical subgroups most likely to benefit, determined from the incidence rate of TF and hospital readmissions. METHODS: Enrolment criteria included the diagnosis of COPD, a smoking history of ≥10 pack-years and ≥ 1 exacerbation in the previous year. Rate ratio (RR) calculations, subgroup analyses and modelling of continuous variables using splines were based on a Poisson regression model, adjusted for exposure time. RESULTS: Azithromycin significantly reduced TF by 24% within 3 m (RR = 0.76, 95%CI:0.59;0.97, p = 0.031) through a 50% reduction in SH (RR = 0.50, 95%CI:0.30;0.81, p = 0.006), which comprised of a 53% reduction in hospital readmissions (RR = 0.47, 95%CI:0.27;0.80; p = 0.007). A significant interaction between the intervention, CRP and blood eosinophil count at hospital admission was found, with azithromycin significantly reducing hospital readmissions in patients with high CRP (> 50 mg/L, RR = 0.18, 95%CI:0.05;0.60, p = 0.005), or low blood eosinophil count (<300cells/μL, RR = 0.33, 95%CI:0.17;0.64, p = 0.001). No differences were observed in treatment response by age, FEV1, CRP or blood eosinophil count in continuous analyses. CONCLUSIONS: This post-hoc analysis of the BACE trial shows that azithromycin initiated at the onset of an infectious COPD exacerbation requiring hospitalization reduces the incidence rate of TF within 3 m by preventing hospital readmissions. In patients with high CRP or low blood eosinophil count at admission this treatment effect was more pronounced, suggesting a potential role for these biomarkers in guiding azithromycin therapy. TRIAL REGISTRATION: ClinicalTrials.gov number. NCT02135354.
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spelling pubmed-68196552019-10-31 Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo – a post-hoc analysis of the BACE randomized controlled trial Vermeersch, Kristina Belmans, Ann Bogaerts, Kris Gyselinck, Iwein Cardinaels, Nina Gabrovska, Maria Aumann, Joseph Demedts, Ingel K. Corhay, Jean-Louis Marchand, Eric Slabbynck, Hans Haenebalcke, Christel Vermeersch, Stefanie Verleden, Geert M. Troosters, Thierry Ninane, Vincent Brusselle, Guy G. Janssens, Wim Respir Res Research BACKGROUND: In the BACE trial, a 3-month (3 m) intervention with azithromycin, initiated at the onset of an infectious COPD exacerbation requiring hospitalization, decreased the rate of a first treatment failure (TF); the composite of treatment intensification (TI), step-up in hospital care (SH) and mortality. OBJECTIVES: (1) To investigate the intervention’s effect on recurrent events, and (2) to identify clinical subgroups most likely to benefit, determined from the incidence rate of TF and hospital readmissions. METHODS: Enrolment criteria included the diagnosis of COPD, a smoking history of ≥10 pack-years and ≥ 1 exacerbation in the previous year. Rate ratio (RR) calculations, subgroup analyses and modelling of continuous variables using splines were based on a Poisson regression model, adjusted for exposure time. RESULTS: Azithromycin significantly reduced TF by 24% within 3 m (RR = 0.76, 95%CI:0.59;0.97, p = 0.031) through a 50% reduction in SH (RR = 0.50, 95%CI:0.30;0.81, p = 0.006), which comprised of a 53% reduction in hospital readmissions (RR = 0.47, 95%CI:0.27;0.80; p = 0.007). A significant interaction between the intervention, CRP and blood eosinophil count at hospital admission was found, with azithromycin significantly reducing hospital readmissions in patients with high CRP (> 50 mg/L, RR = 0.18, 95%CI:0.05;0.60, p = 0.005), or low blood eosinophil count (<300cells/μL, RR = 0.33, 95%CI:0.17;0.64, p = 0.001). No differences were observed in treatment response by age, FEV1, CRP or blood eosinophil count in continuous analyses. CONCLUSIONS: This post-hoc analysis of the BACE trial shows that azithromycin initiated at the onset of an infectious COPD exacerbation requiring hospitalization reduces the incidence rate of TF within 3 m by preventing hospital readmissions. In patients with high CRP or low blood eosinophil count at admission this treatment effect was more pronounced, suggesting a potential role for these biomarkers in guiding azithromycin therapy. TRIAL REGISTRATION: ClinicalTrials.gov number. NCT02135354. BioMed Central 2019-10-29 2019 /pmc/articles/PMC6819655/ /pubmed/31665017 http://dx.doi.org/10.1186/s12931-019-1208-6 Text en © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Vermeersch, Kristina
Belmans, Ann
Bogaerts, Kris
Gyselinck, Iwein
Cardinaels, Nina
Gabrovska, Maria
Aumann, Joseph
Demedts, Ingel K.
Corhay, Jean-Louis
Marchand, Eric
Slabbynck, Hans
Haenebalcke, Christel
Vermeersch, Stefanie
Verleden, Geert M.
Troosters, Thierry
Ninane, Vincent
Brusselle, Guy G.
Janssens, Wim
Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo – a post-hoc analysis of the BACE randomized controlled trial
title Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo – a post-hoc analysis of the BACE randomized controlled trial
title_full Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo – a post-hoc analysis of the BACE randomized controlled trial
title_fullStr Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo – a post-hoc analysis of the BACE randomized controlled trial
title_full_unstemmed Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo – a post-hoc analysis of the BACE randomized controlled trial
title_short Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo – a post-hoc analysis of the BACE randomized controlled trial
title_sort treatment failure and hospital readmissions in severe copd exacerbations treated with azithromycin versus placebo – a post-hoc analysis of the bace randomized controlled trial
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819655/
https://www.ncbi.nlm.nih.gov/pubmed/31665017
http://dx.doi.org/10.1186/s12931-019-1208-6
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